Tobacco Dependence and Reduction Thereof.
In recent years, with the recognition of the harmful effects of tobacco smoking, there have been numerous campaigns and programs by governmental agencies and various health groups and other interested organizations to disseminate information about the adverse health effects resulting from tobacco smoking. Moreover, and as a result of this recognition of the harmful effects, there have been many programs directed to attempts in reducing smoking incidence.
Nicotine is an organic compound and is the principal alkaloid of tobacco. Nicotine is the chief active ingredient in the tobacco used in cigarettes, cigars, snuff and the like. Nicotine is also an addictive drug, though, and smokers characteristically display a strong tendency to relapse after having successfully stopped smoking for a time. Nicotine is the world's second most used drug, after caffeine from coffee and tea.
The main problem with tobacco smoking is its enormous implications on health. Today it is estimated that smoking-related diseases cause some 3-4 million deaths per year. In the U.S. Surgeon General's 1988 report on The Health Consequences of Smoking, it was estimated that in the U.S. alone about 300.000 deaths are caused each year by diseases related to cigarette smoking. In fact, excessive smoking is now recognized as one of the major health problems throughout the world. This grim consequence of tobacco smoking has urged many medical associations and health authorities to take very strong actions against the use of tobacco.
Even though tobacco smoking is decreasing in many developed countries today it is hard to see how the societies could get rid of the world's second most used drug.
The most advantageous thing a heavy smoker can do is to reduce or preferably even stop smoking completely. Experience shows, however, that most smokers find this extremely difficult since, mostly, tobacco smoking results in a dependence disorder or craving. The WHO has in its International Classification of Disorders a diagnosis called Tobacco Dependence. Others, like the American Psychiatric Association call the addiction Nicotine Dependence. It is generally accepted that these difficulties to stop smoking result from the fact that those heavy smokers are dependent on nicotine. The most important risk factors are, however, substances that are formed during the combustion of tobacco, such as carcinogenic tar products, carbon monoxide, aldehydes, and hydrocyanic acid.
Effects of Nicotine
The administration of nicotine can give satisfaction and the usual method is by smoking, either by smoking e.g., a cigarette, a cigar or a pipe, or by snuffing or chewing tobacco. However, smoking has health hazards and it is therefore desirable to formulate an alternative manner of administering nicotine in a pleasurable manner that can be used to facilitate withdrawal from smoking and/or used as a replacement for smoking.
Upon smoking of a cigarette, nicotine is quickly absorbed into the smoker's blood and reaches the brain within around ten seconds after inhalation. The quick uptake of nicotine gives the consumer a rapid satisfaction, or kick. The satisfaction, then, lasts during the time of smoking the cigarette and for a period of time thereafter. The poisonous, toxic, carcinogenic, and addictive nature of smoking has provided efforts for methods, compositions and devices, which help in breaking the habit of smoking.
Nicotine is an addictive poisonous alkaloid C5H4NC4H7NCH3, derived from the tobacco plant. Nicotine is also used as an insecticide. Approximately forty milligrams of nicotine may kill an adult (Merck Index).
Nicotine Replacement Products and Prior Art
One way to reduce smoking is to provide nicotine in a form or manner other than by smoking and some products have been developed to fulfill this need. Nicotine containing formulations are currently the dominating treatments for tobacco dependence.
The success in achieving reduction in the incidence of smoking has been relatively poor using presently known products. State of the art involves both behavioral approaches and pharmacological approaches. More than 80% of the tobacco smokers who initially quit smoking after using some behavioral or pharmacological approach to singly reduce smoking incidence generally relapse and return to the habit of smoking at their former rate of smoking within about a one year's period of time.
As an aid for those who are willing to stop smoking there are several ways and forms of nicotine replacement products available on the market, such as nicotine chewing gums according to U.S. Pat. No. 3,845,217. Several methods and means have been described for diminishing the desire of a subject to use tobacco, which comprises the step of administering to the subject nicotine or a derivative thereof as described in e.g. U.S. Pat. No. 5,939,100 (nicotine containing microspheres) and U.S. Pat. No. 4,967,773 (nicotine containing lozenge).
The use of skin patches for transdermal administration of nicotine has been reported (Rose, in Pharmacological Treatment of Tobacco Dependence, (1986) pp. 158-166, Harvard Univ. Press). Nicotine-containing skin patches that are in wide use today can cause local irritation and the absorption of nicotine is slow and affected by cutaneous blood flow.
Nicotine-containing nose drops have been reported (Russell et al., British Medical Journal, Vol. 286, p. 683 (1983); Jarvis et al., British Journal of Addiction, Vol. 82, p. 983 (1987)). Nose drops, however, are difficult to administer and are not convenient for use at work or in other public situations. Administration of nicotine by way of delivery directly into the nasal cavity by spraying is known from U.S. Pat. No. 4,579,858, DE 32 41 437 and U.S. Pat. No. 5,656,255. There may, though, be local nasal irritation with use of nasal nicotine formulations. The difficulty in administration also results in unpredictability of the dose of nicotine administered.
Mouth sprays comprising nicotine are known in the art, e.g., according to U.S. Pat. No. 6,024,097 wherein is disclosed a method of assisting a smoker in giving up the smoking habit whereby is used a plurality of aerosol dispensers comprising progressively lesser concentrations of nicotine. The aerosol is intended to be administered into the mouth. The liquid in the dispensers essentially consists of nicotine and alcohol. GB 2 030 862 discloses a nicotine-containing aerosol for oral administration.
A similar mouth spray is disclosed in U.S. Pat. No. 5,810,018, whereby in addition the aerosol comprises progressively greater concentrations of at least one selected stimulant.
U.S. Pat. No. 6,413,496 discloses an aerosol device with an active and a propellant. The device may be used for e.g., sublingual administration. Nicotine is mentioned as an active in a long “laundry list” of drugs. There are though no examples on nicotine formulations.
U.S. Pat. No. 5,955,098 discloses a non-polar buccal aerosol spray using a non-polar solvent. Nicotine is mentioned as one useful active in this spray.
Inhaling devices resembling a cigarette are known for uptake of nicotine vapors mainly buccally is suggested in U.S. Pat. No. 5,167,242. A proposal on a nicotine aerosol is disclosed in DE 32 41 437. Newman et al., J Pharma Sci, Vol 85, No 9, September 1996 discloses highly ethanolic systems for administering the asthma medication flunisolide as aerosol to the lungs. Possible utility of these systems for delivery of nicotine is though not discussed. Buffering of the medication for facilitating pulmonary delivery is not discussed.
U.S. Pat. No. 4,953,572 and U.S. Pat. No. 4,920,989 disclose one and the same nicotine-containing aerosol intended for inhalation.
Burch et al. disclose in Am Rev Respir Dis 189; 140:955-957 pulmonary inhalation of nicotine in conjunction with buccal deposition of a nicotine formulation having pH 10.
Andrus et al. disclose in Can Respir J Vol 6 No 6:509-512 a nicotine microaerosol inhaler wherein nicotine is present in a non-pH regulated formulation comprising ethanol and a propellant.
Hitherto is though not known any pharmaceutical formulations or systems that efficiently may administer nicotine for uptake mainly in the lungs in order to mimic the nicotine uptake provided by smoking without the adverse effects caused by smoking.
Problems to be Solved
The captioned means and methods do not satisfy the craving that certain users of tobacco experience. Specifically these means and methods generally do not provide for a sufficiently rapid uptake of nicotine without adverse effects. In nicotine replacement therapy, NRT, many smokers wish to obtain a head rush or very quick onset of nicotine similar to the one obtained by inhaling cigarette smoke. None of hitherto known NRT means may provide for this.
In light of the aforementioned problem there is a strong need and interest to develop formulations, means and methods for the administration of nicotine to provide a very fast satisfaction to a person craving for nicotine or to provide a sense of smoking satisfaction without smoking, whereby also may be avoided problems associated with the prior art means and methods. The present invention addresses said need and interest.